Many of the diphosphonic acid compounds that have been developed mainly as drugs for treatment of bone metabolic diseases thus far have an action to inhibit bone destruction, and have been expected to inhibit bone destruction during the occurrence of arthritis such as chronic articular rheumatism. Although compounds having a diphosphonic acid structure are disclosed in Japanese Unexamined Patent Publication (Kokai) No. 59-42395, Japanese Unexamined Patent Publication (Kokai) No. 2-22285, Japanese Unexamined Patent Publication (Kokai) No. 3-77894 and Japanese Unexamined Patent Publication (Kokai) No. 60-174792, these diphosphonic acid compounds are primarily focused on inhibition of bone resorption. Although these compounds are effective as therapeutic drugs for bone metabolic disorders, they are still not adequate for treatment of chronic articular rheumatism.
In order for diphosphonic acid compounds to be used in the treatment of chronic articular rheumatism and so forth, a new drug is desired that, in addition to having an action to inhibit bone resorption, also has other, more effective actions, including inhibition of Interleukin-1 (abbreviated as IL-1), which is a mediator of inflammations, as well as inhibition of cell damage caused by activated neutrophils and macrophages.
IL-1 is known to be a mediator involved in pyrexia and inflammation, and its inhibitory agent is expected to be useful as an antiinflammatory drug. However, similar to many other cytokines, IL-1 is considered to mainly act locally. Although numerous substances have been reported to inhibit IL-1 in vitro, antiinflammatory drugs having action that allows adequate improvement of the disease state by actually inhibiting IL-1 in vivo have not yet been developed. In addition, invasion of activated neutrophils and macrophages at the site of inflammation have been observed during inflammations. Although the active oxygen produced by these blood cells has an action of heterogenous digestion, in cases where an inflammation has become chronic, these cells are known to damage normal tissue as well. Thus, compounds having both an IL-1 inhibiting action and antioxidative action are considered to be useful as not only antiinflammatory drugs, but also against autoimmune diseases such as chronic articular rheumatism, as well as organ disorders, such as those in the brain and liver, which occur during ischemia.